Quality assurance & pharmacopeial assay Flashcards
What are the sources of impurities?
- Raw materials
- Method of manufacture
- Atmospheric contaminant
- Manufacturing hazards
- Inadequate storage
Sources of impurities in method of manufacture
- Reagents employed in process
- Reagents added to remove other impurities
- Solvents
- Reaction vessels
Sources of impurities in manufacturing hazards
- Particulate contamination
- Process errors
- Cross-contamination
- Microbial contamination
- Packing errors
Sources of impurities in inadequate storage
- Filth
- Chemical instability
3, Reaction with container materials - Physical changes
- Temperature effects
What are limit tests?
Quantitative or semi-quantitative tests designed to identify and control small quantities of impurity
which may be present in the drug substance
Comparison methods
A standard containing a definite amount of impurity
is set up at the same time and same conditions as the test experiment.
Official limits for which impurities are based on comparison methods?
Chloride
Sulphates
Iron
Heavy metals
Total Ash method
A measure of the total ash remaining after incineration
What does high ash value indicate?
Contamination, substitution or carelessness in preparing the crude drugs for marketing Inorganic salts of carbonates, phosphate or silicates of sodium, potassium calcium and magnesium
Infrared Absorption Test for identification
Compare the IR spectrum of the test sample and the USP reference standard
Types of limit tests
a. Limits of insoluble matter
b. Limits of soluble matters
c. Limits of moisture, volatile matters, and residual solvents
d. Limits of non-volatile matter
e. Loss on ignition
- Limits of residue on ignition
- Ash values
e. Precipitation methods
What is the significance of IR spectrum?
Stretching and bending of bonds in different functional groups to the structure of the analyte
UV Absorption Test for identification
UV absorption measured of a test solution and a standard solution, using a 1cm cell, over 200-400nm
Significance of UV spectra
- Determine the absorptivities and or absorbance ratios as indicated in the monograph
- The requirements are met if the UV absorption spectra of the test and standard solutions exhibit maxima and minima at the same wavelength and the absorptivities and/or absorbance ratios are within specified limits.
TLC Test for identification
The Rf value of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution – indicates a positive identity to the Standard reference
Advantages of Titrimetric analysis
- Capable of high degree of precision and accuracy
- Methods are generally robust
- Analyses can be automated and cheap to perform
Limitations of Titrimetric analysis
- Method may not be selective
- Time-consuming
- Require large amount s of sample and reagents
Types of Titrimetric analysis
1. Direct acid/base titration in aqueous phase
2. Indirect titration in aqueous phase
3. Argentometric titration
4. Complexometric titration
5. Redox Titration
6. Non-aqueous Titration
7. Potentiometric Titration
What are primary standards
Stable chemical compounds that are available in high purity and that can be used to standardize the standard solutions used in titrations
What is used to determine correction factor?
Primary standards
Correction factor
Ratio of (Actual concentration)/(Desired (or nominal)concentration).
What does the value of correction factor signifies?
f < 1: the prepared solution is of lower concentration that what was desired
f > 1: the prepared solution is of higher concentration that what was desired
f = 1: the prepared solution is prepared precisely to the desired
When is indirect (back) titration used?
a) Volatile substance (e.g. ammonia, volatile oil)
b) Insoluble substances (e.g. CaCO3)
c) Substances for which a quantitative reaction proceeds rapidly only in excess of a reagent (e.g. lactic acid)
d) Substances which require heating with a volumetric reagent during the determination in which a decomposition or loss of the reactants or products would occur in the process (e.g. aspirin)
What is necessary during back titration involving heating a liquid containing excess of standard alkali,
cooling and back titrate the excess.
Blank titration - heating and cooling may cause apparent changes in strength of excess reagent
HPLC analysis always requires a _________.
Calibration curve
(HPLC) Calibration against internal standard which should _____?
- Be closely related in structure to the analyse
- Be stable
- Be chromo
QA vs QC
- QA is proactive, QC results in reactive steps to correct issue
- QA is process oriented, QC is product oriented
- QA controls overall (at system level), QC controls parts in the process
- QA activities create high quality products, QC verifies products in post-manufacture stage
- QA involves entire team, QC by dedicated trained personnel
5 key components of GMP (1)
Raw/starting materials used in manufacturing must be pure.
5 key components of GMP (2)
Premises and equipment used for manufacturing must be maintained for operational readiness.
5 key components of GMP (3)
People involved in the manufacturing process must be trained to competent level.
5 key components of GMP (4)
The manufacturing procedures must use the latest technology and science.
5 key components of GMP (5)
Processes must be documented to show compliance.
